Identification of progenitor CD4 T cells that support response to chronic antigen

摘要 控制慢性感染或感染需要CD4和CD8T细胞的持久免疫反应 肿瘤。在过去的几年里，多项独立研究已经确定了类祖细胞或干细胞的子集- 如TCF-1、PD-1、CD8、T细胞在慢性病毒感染和肿瘤中的表达。这些祖细胞CD8 T细胞 继续产生新的效应器CD8T细胞以支持CD8T细胞对持久性抗原的长期反应 (AGS)。它们还能够通过免疫检查点阻断而引发强大的效应器反应 靶向PD-1到PD-L1的相互作用。然而，目前仍不清楚CD4T细胞如何对持续性 AG是否被维持，或者是否有相当于TCF-1的特化的祖细胞样CD4T细胞亚群 祖细胞CD8T细胞的存在是为了支持CD4T细胞反应的持久性或对PD-1阻断的反应。 我们已经发现转录因子BCL6对于持久的CD4T细胞效应器应答是必不可少的 慢性LCMV感染，意味着在慢性疾病面前存在类似的祖细胞CD4T细胞 抗原刺激。我们建议确定这样的CD4T细胞群并进行初步的 独特的CD4T细胞亚群的特征。

Abstract Durable immune response by both CD4 and CD8 T cells is required for the control of chronic infection or tumors. In the past few years, multiple independent studies have identified a subset of progenitor-like or stem- like TCF-1+ PD-1+ CD8 T cells in both chronic viral infections and tumors. These progenitor CD8 T cells continue generating new effector CD8 T cells to support long-term CD8 T cell responses to persisting antigens (Ags). They are also capable of eliciting robust effector responses by the immune checkpoint blockade targeting the PD-1 to PD-L1 interaction. However, it remains unknown how CD4 T cell responses to persistent Ag are maintained, or whether a specialized subset of progenitor-like CD4 T cells equivalent to TCF-1+ progenitor CD8 T cells exists to support the durability of CD4 T cell response or respond to the PD-1 blockade. We have found that the transcription factor BCL6 is essential for the durable CD4 T cell effector response to chronic LCMV infection, implying that an analogous progenitor CD4 T cells are present in the face of chronic antigen stimulation. We propose to identify such a CD4 T cell population and conduct the initial characterization of the unique CD4 T cell subset.